Formulation and clinical investigation of optimized vinpocetine lyoplant-tabs: new strategy in development of buccal solid dosage form

BACKGROUND: This work aimed to develop a new solid dosage formulation of vinpocetine (VPN) in the form of buccal freeze-dried pullulan-based tablets (lyoplant-tabs) loaded with physically modified drug binary system. METHODS: Different polyvinyl pyrrolidone (PVP) grades were studied to prepare an efficient VPN binary system characterized by enhanced equilibrium saturation solubility, solubilization efficiency, thermodynamic stability, and permeation through oral mucosal cell lines. The concentrations of pullulan and swelling-aid polymer that affect the quality attributes of lyoplant-tabs were optimized. Clinical pharmacokinetics study on human volunteers for the optimized lyoplant-tabs compared to marketed product was accomplished. RESULTS: A promising drug binary system with polyvinyl pyrrolidone vinyl acetate (PVP-VA64) utilizing the lyophilization technique was developed. Solid-state characterization confirmed transformation of VPN completely into the amorphous form. The concentrations of pullulan and swelling-aid polymer were significantly affecting the characteristics of the tablets. Compared to the commercial VPN tablets, pullulan-based buccal tablets demonstrated enhancement in the studied pharmacokinetic parameters with positive impact on the drug bioavailability. CONCLUSION: These VPN lyoplant-tabs containing lyophilized PVP-VA64-VPN binary system can be considered as an alternative to currently available marketed tablets; however, further preclinical investigations using large number of volunteers are required.